Journal
TETRAHEDRON LETTERS
Volume 59, Issue 30, Pages 2904-2908Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tetlet.2018.06.040
Keywords
Anticancer activity; Thiosugar; NHC-gold complex; Thioredoxin reductase
Categories
Funding
- UCD School of Chemistry
- National Cancer Institute (NCI) at Maryland USA
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Gold(I) complexes containing stabilising ligands such as phosphines or N-heterocyclic carbenes (NHCs) are known to be inhibitors of the enzyme thioredoxin reductase (TrxR) and therefore act as potential apoptosis-inducing anticancer drug candidates. The conjugation of biomolecules overexpressed in cancer cells to the gold complexes makes them semi-targeted metabolites. Auranofin, an anti-arthritis agent, encompasses this property and exhibits anti-tumour activities. The synthesis, characterization and biological evaluation of four novel N-heterocyclic carbene-gold(I)-thiosugar complexes derived from glucose, lactose and galactose is reported. The reactions of 1,3-dibenzy1-4,5-diphenyl-imidazol-2-ylidene gold(I) chloride (NHC*-Au-C1) with pre-synthesized glycosyl thiols under mildly basic conditions gave the desired NHC-Au-thiosugar complexes in high to excellent yields (79-91%). The complexes retain the strong and redox-active Au-S bond contained in Auranofin. All complexes showed good solubility in biological media and were tested against the NCI 60 cancer cell panel for cytotoxicity. The synthesized NHC*-Au derivatives showed good activity in the medium to low micromolar region, while complex 2 showed activity in the low micromolar to nanomolar region against the tested cell lines. To provide a theoretical structure of 4, computational calculations were carried out based on the crystal structures of NHC-Au-SCN and NHC-Au-S-C6H4OMe. (C) 2018 Published by Elsevier Ltd.
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